A man accused of murdering his wife and co-workers leads the CSIs on a wild ride through a busy casino, eventually barricading himself and a hostage in a casino hotel room. The CSIs process the evidence from the crime scene to determine whether or not the man acted alone or had an accomplice. One of the CSIs eventually steps in as a hostage negotiator, putting himself in danger.

In the season finale, the CSIs wait by the bedside of one of their own when he's shot in the line of duty. One CSI faces a hard choice by having the power of attorney over their injured friend and colleague. Meanwhile, the team also investigates the strange way of life of one man when he is found decapitated by a train.

Catherine testifies in a murder trial in which a man is accused of murdering his own mother three years ago, but the suspect is found not guilty. Catherine, however, believes he did commit the crime and that he may also have killed two other people, so she sets out to find the other victims. Grissom prepares to leave on a four-week sabbatical.

CSI investigates the death of a little girl whose identity remains unknown.

Langston and Riley are taken hostage during the aftermath of a shootout in an usually calm Las Vegas community.

When the CSI team investigates the brutal murder of a family, they trace the killer to the house next door, which might belong to the "Dr. Jekyll" serial killer.